A data-based mathematical modelling study to quantify the effects of ciprofloxacin and ampicillin on the within-host dynamics of <i>Salmonella enterica</i> during treatment and relapse.
Journal of the Royal Society, Interface
The Royal Society
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Vlazaki, M., Rossi, O., Price, D. J., McLean, C., Grant, A., Mastroeni, P., & Restif, O. (2020). A data-based mathematical modelling study to quantify the effects of ciprofloxacin and ampicillin on the within-host dynamics of <i>Salmonella enterica</i> during treatment and relapse.. Journal of the Royal Society, Interface, 17 (168), 20200299. https://doi.org/10.1098/rsif.2020.0299
Antibiotic therapy has drastically reduced the mortality and sequelae of bacterial infections. 33 From naturally-occurring to chemically-synthesised, different classes of antibiotics have been 34 successfully used without detailed knowledge of how they affect bacterial dynamics in vivo. 35 However, a proportion of patients receiving antimicrobial therapy develop recrudescent 36 infections post-treatment. Relapsing infections are attributable to incomplete clearance of 37 bacterial populations following antibiotic administration; the metabolic profile of this 38 antibiotic-recalcitrant bacterial subpopulation, the spatiotemporal context of its emergence and 39 the variance of antibiotic-bacterial interactions in vivo remain unclear. Here, we develop and 40 apply a mechanistic mathematical model to data from a study comparing the effects of 41 ciprofloxacin and ampicillin on the within-host dynamics of Salmonella enterica serovar 42 Typhimurium in murine infections. Using the inferential capacity of our model, we show that 43 the antibiotic-recalcitrant bacteria following ampicillin, but not ciprofloxacin, treatment belong 44 to a non-replicating phenotype. Aligning with previous studies, we independently estimate that 45 the lymphoid tissues and spleen are important reservoirs of non-replicating bacteria. Finally, 46 we predict that post-treatment the progenitors of the non-growing and growing bacterial 47 populations replicate and die at different rates. Ultimately, the liver, spleen and mesenteric 48 lymph nodes are all repopulated by progenitors of the previously non-growing phenotype in 49 ampicillin-treated mice.
Animals, Humans, Mice, Salmonella enterica, Recurrence, Ampicillin, Ciprofloxacin, Anti-Bacterial Agents, Microbial Sensitivity Tests, Models, Theoretical
Bursary from Cambridge Mathematical Placements
External DOI: https://doi.org/10.1098/rsif.2020.0299
This record's URL: https://www.repository.cam.ac.uk/handle/1810/306950
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